He returned to a diplomatic career in 1937, serving as the final League of Nations High Commissioner for the Free City of Danzig from 1937 to 1939. In that position, he aimed to maintain the international status of Danzig guaranteed by the League of Nations, which brought him into contact with a number of prominent Nazis as he attempted to stave off increasing German demands. The mission eventually ended unsuccessfully with the invasion of Poland and German annexation of Danzig.

Following this period as High Commissioner, he returned to his professorship in Geneva for the rest of World War II (1939–1945). While in that position, he was also active in a leading role in the ICRC, traveling to Germany several times to negotiate for better treatment of civilians and prisoners, in part using the contacts gained during his two years as High Commissioner in Danzig.

After the war, he became President of the ICRC, serving from 1945 to 1948. Organizationally, he increased the integration of the international Red Cross institutions and the national Red Cross Societies. Politically, his term was controversial as he maintained the ICRC's existing policy of strict neutrality in international disputes, which led to the ICRC refusing to officially condemn the Nazis as their atrocities came to light. His strong anti-Communism even led to him considering Nazism the lesser evil. During this period, he simultaneously served from 1945 to 1949 as the Swiss envoy in Paris.

Burckhardt was "a close friend and admirer of Hitler" and was kept informed of the Final Solution as early as 1941. Under his leadership, the ICRC "served as a tool of Nazi extermination policy", according to Israeli historian Livia Rothkirchen. The Red Cross' stance during the war did not fully come to light until it opened its archives from the period in 1994.[1]

After 1949, he returned to his academic career, publishing a number of books on history over the next several decades. In 1954 he was awarded the Peace Prize of the German Book Trade. He died in 1974 in Vinzel. His wife died in 1989.